Science

To err is human

by reestheskin on 01/02/2021

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What my retraction taught me

In the middle of the pandemic, I got an e-mail asking whether I had access to data from the experiments behind a paper I’d published in 2014. Three months later, I requested that the paper be retracted. The experience has not left me bitter: if anything, it brought me back to my original motivation for doing research.

This is a disarmingly honest piece (in the journal Nature) about how mistakes in the analysis of complicated data sets caused inappropriate conclusions, leading, in this case, to a retraction of a manuscript.

As a student, I was even told never to attempt to replicate before I publish. That is not a career I would want — luckily, my PhD adviser taught me the opposite.

John Ziman warned over 20 years ago in Real Science that we were entering post-academic science. Here are some words of his from an article in Nature.

What is more, science is no longer what it was when [Robert] Merton first wrote about it. The bureaucratic engine of policy is shattering the traditional normative frame. Big science has become a novel way of life, with its own conventions and practices. What price now those noble norms? Tied without tenure into a system of projects and proposals, budgets and assessments, how open, how disinterested, how self-critical, how riskily original can one afford to be?

As the economists are fond of saying: institutions matter. As do incentives. Precious metals can be corrupted, and money — in the short term — made.

Winnowing MMXXI

by reestheskin on 21/01/2021

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STEM stupidity

Stupid | No Mercy / No Malice

Mark Zuckerberg is what happens when you replace civics with computer science.


Eureka… if not the bath

New Year Monday Note. | Jean-Louis Gassée | Jan, 2021

In the shower, all ideas look good.


Post-modem

Universities challenged: critical theory and culture wars | Financial Times

A comment about the above article:

As a full professor in a similar situation, a humanities department in a British teaching factory (sorry major research university) I completely agree with Musidorus.


Girl-talk

The Economist | Awesome, weird and everything else

Ironically, some old gender stereotypes may now be helping girls. When girls are toddlers they are read to more than boys. Their fathers are five times more likely to sing or whistle to them and are more likely to speak to them about emotions, including sadness. Their mothers are more likely to use complex vocabulary with them. Most of this gives girls a leg up in a world that increasingly prizes “soft skills”. Girls still have less leisure time than boys, but nowadays that is primarily because they spend more time on homework and grooming, rather than an unfair division of chores. And in the time left for themselves they have far more freedom.

The one good thing about COVID-19 is that it’s good for nature and the environment and dolphins,” says Sarah, “but I wish it wouldn’t kill so many people in the process.”


COVID-19 aware

David Hume — Wikipedia

He had little respect for the professors of his time, telling a friend in 1735 that “there is nothing to be learnt from a Professor, which is not to be met with in Books”. He did not graduate.

Nor did I ever submit my PhD. As David Hubel once said, the great advantage of an MD degree was (then) being able to avoid having to gain a PhD credential.

Academic lives

by reestheskin on 11/01/2021

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Originality is usually off track

How mRNA went from a scientific backwater to a pandemic crusher | WIRED UK

For decades, Katalin Karikó’s work into mRNA therapeutics was overlooked by her colleagues. Now it’s at the heart of the two leading coronavirus vaccines

By the mid 1990s, Karikó’s bosses at UPenn had run out of patience. Frustrated with the lack of funding she was generating for her research, they offered the scientist a bleak choice: leave or be demoted. It was a demeaning prospect for someone who had once been on the path to a full professorship. For Karikó’s dreams of using mRNA to create new vaccines and drugs for many chronic illnesses, it seemed to be the end of the road… ”It was particularly horrible as that same week, I had just been diagnosed with cancer,” said Karikó. “I was facing two operations, and my husband, who had gone back to Hungary to pick up his green card, had got stranded there because of some visa issue, meaning he couldn’t come back for six months. I was really struggling, and then they told me this.”

Karikó has been at the helm of BioNTech’s Covid-19 vaccine development. In 2013, she accepted an offer to become Senior Vice President at BioNTech after UPenn refused to reinstate her to the faculty position she had been demoted from in 1995. “They told me that they’d had a meeting and concluded that I was not of faculty quality,” she said. ”When I told them I was leaving, they laughed at me and said, ‘BioNTech doesn’t even have a website.’”


Being at the bottom of things

Knuth versus Email

Donald Knuth is a legend amongst computer scientists.

I have been a happy man ever since January 1, 1990, when I no longer had an email address. I’d used email since about 1975, and it seems to me that 15 years of email is plenty for one lifetime.Email is a wonderful thing for people whose role in life is to be on top of things. But not for me; my role is to be on the bottom of things. What I do takes long hours of studying and uninterruptible concentration. I try to learn certain areas of computer science exhaustively; then I try to digest that knowledge into a form that is accessible to people who don’t have time for such study. [emphasis added]

On retirement:

I retired early because I realized that I would need at least 20 years of full-time work to complete The Art of Computer Programming (TAOCP), which I have always viewed as the most important project of my life.

Being a retired professor is a lot like being an ordinary professor, except that you don’t have to write research proposals, administer grants, or sit in committee meetings. Also, you don’t get paid.

My full-time writing schedule means that I have to be pretty much a hermit. The only way to gain enough efficiency to complete The Art of Computer Programming is to operate in batch mode, concentrating intensively and uninterruptedly on one subject at a time, rather than swapping a number of topics in and out of my head. I’m unable to schedule appointments with visitors, travel to conferences or accept speaking engagements, or undertake any new responsibilities of any kind.


On Keeping Your Soul

John Baez is indeed a relative of that other famous J(oan) Baez. I used to read his blog avidly

The great challenge at the beginning of ones career in academia is to get tenure at a decent university. Personally I got tenure before I started messing with quantum gravity, and this approach has some real advantages. Before you have tenure, you have to please people. After you have tenure, you can do whatever the hell you want — so long as it’s legal, and you teach well, your department doesn’t put a lot of pressure on you to get grants. (This is one reason I’m happier in a math department than I would be in a physics department. Mathematicians have more trouble getting grants, so there’s a bit less pressure to get them.)

The great thing about tenure is that it means your research can be driven by your actual interests instead of the ever-changing winds of fashion. The problem is, by the time many people get tenure, they’ve become such slaves of fashion that they no longer know what it means to follow their own interests. They’ve spent the best years of their life trying to keep up with the Joneses instead of developing their own personal style! So, bear in mind that getting tenure is only half the battle: getting tenure while keeping your soul is the really hard part. [emphasis added]


On the hazards of Epistemic trespassing

Scientists fear that ‘covidization’ is distorting research

Scientists straying from their field of expertise in this way is an example of what Nathan Ballantyne, a philosopher at Fordham University in New York City, calls “epistemic trespassing”. Although scientists might romanticize the role and occasional genuine insight of an outsider — such as the writings of physicist Erwin Shrödinger on biology — in most cases, he says, such academic off-piste manoeuvrings dump non-experts head-first in deep snow. [emphasis added]

But I do love the language…


On the need for Epistemic trespassing

Haack, Susan, Not One of the Boys: Memoir of an Academic Misfit

Susan Haack is a wonderfully independent English borne philosopher who loves to roam, casting light wherever her interest takes her. 

Better ostracism than ostrichism

Moreover, I have learned over the years that I am temperamentally resistant to bandwagons, philosophical and otherwise; hopeless at “networking,” the tit-for-tat exchange of academic favors, “going along to get along,” and at self-promotion

 

That I have very low tolerance for meetings where nothing I say ever makes any difference to what happens; and that I am unmoved by the kind of institutional loyalty that apparently enables many to believe in the wonderfulness of “our” students or “our” department or “our” school or “our” university simply because they’re ours.

 

Nor do I feel what I think of as gender loyalty, a sense that I must ally myself with other women in my profession simply because they are women—any more than I feel I must ally myself with any and every British philosopher simply because he or she is British. And I am, frankly, repelled by the grubby scrambling after those wretched “rankings” that is now so common in philosophy departments. In short, I’ve never been any good at academic politicking, in any of its myriad forms.

 

And on top of all this, I have the deplorable habit of saying what I mean, with neither talent for nor inclination to fudge over disagreements or muffle criticism with flattering tact, and an infuriating way of seeing the funny side of philosophers’ egregiously absurd or outrageously pretentious claims — that there are no such things as beliefs, that it’s just superstitious to care whether your beliefs are true, that feminism obliges us to “reinvent science and theorizing,” and so forth.

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Citizens of nowhere trespassing…

The Economist | Citizen of the world

From a wonderful article in the Economist

As Michael Massing shows vividly in “Fatal Discord: Erasmus, Luther and the Fight for the Western Mind” (2018), the growing religious battle destroyed Erasmianism as a movement. Princes had no choice but to choose sides in the 16th-century equivalent of the cold war. Some of Erasmus’s followers reinvented themselves as champions of orthodoxy. The “citizen of the world” could no longer roam across Europe, pouring honeyed words into the ears of kings. He spent his final years holed up in the free city of Basel. The champion of the Middle Way looked like a ditherer who was incapable of making up his mind, or a coward who was unwilling to stand up to Luther (if you were Catholic) or the pope (if you were Protestant).

The test of being a good Christian ceased to be decent behaviour. It became fanaticism: who could shout most loudly? Or persecute heresy most vigorously? Or apply fuel to the flames most enthusiastically?

And in case there is any doubt about what I am talking about.

In Britain, Brexiteers denounce “citizens of the world” as “citizens of nowhere” and cast out moderate politicians with more talent than they possess, while anti-Brexiteers are blind to the excesses of establishment liberalism. In America “woke” extremists try to get people sacked for slips of the tongue or campaign against the thought crimes of “unconscious bias”. Intellectuals who refuse to join one camp or another must stand by, as mediocrities are rewarded with university chairs and editorial thrones. [emphasis added]

As Erasmus might have said: ‘Amen’.

On rejection by editors and society

by reestheskin on 16/11/2020

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The history of science is the history of rejected ideas (and manuscripts). One example I always come back to is the original work of John Wennberg and colleagues on spatial differences in ‘medical procedures’ and the idea that it is not so much medical need that dictates the number of procedures, but that it is the supply of medical services. Simply put: the more surgeons there are, the more procedures that are carried out1. The deeper implication is that many of these procedures are not medically required — it is just the billing that is needed: surgeons have mortgages and tuition loans to pay off. Wennberg and colleagues at Dartmouth have subsequently shown that a large proportion of the medical procedures or treatments that doctors undertake are unnecessary2.

Wennberg’s original manuscript was rejected by the New England Journal of Medicine (NEJM) but subsequently published in Science. Many of us would rate Science above the NEJM, but there is a lesson here about signal and noise, and how many medical journals in particular obsess over procedure and status at the expense of nurturing originality.

Angus Deaton and Anne Case, two economists, the former with a Nobel Prize to his name, tell a similar story. Their recent work has been on the so-called Deaths of Despair — where mortality rates for subgroups of the US population have increased3. They relate this to educational levels (the effects are largely on those without a college degree) and other social factors. The observation is striking for an advanced economy (although Russia had historically seen increased mortality rates after the collapse of communism).

Coming back to my opening statement, Deaton is quoted in the THE

The work on “deaths of despair” was so important to them that they [Deaton and Case] joined forces again as research collaborators. However, despite their huge excitement about it, their initial paper, sent to medical journals because of its health focus, met with rejections — a tale to warm the heart of any academic whose most cherished research has been knocked back.

When the paper was first submitted it was rejected so quickly that “I thought I had put the wrong email address. You get this ping right back…‘Your paper has been rejected’.” The paper was eventually published in Proceedings of the National Academy of Sciences, to a glowing reception. The editor of the first journal to reject the paper subsequently “took us for a very nice lunch”, adds Deaton.

Another medical journal rejected it within three days with the following justification

The editor, he says, told them: “You’re clearly intrigued by this finding. But you have no causal story for it. And without a causal story this journal has no interest whatsoever.”

(‘no interest whatsoever’ — the arrogance of some editors).

Deaton points out that this is a problem not just for medical journals but in economics journals, too; he thinks the top five economics journals would have rejected the work for the same reason.

“That’s the sort of thing you get in economics all the time,” Deaton goes on, “this sort of causal fetish… I’ve compared that to calling out the fire brigade and saying ‘Our house is on fire, send an engine.’ And they say, ‘Well, what caused the fire? We’re not sending an engine unless you know what caused the fire.’

It is not difficult to see the reasons for the fetish on causality. Science is not just a loose-leaf book of facts about the natural or unnatural world, nor is it just about A/B testing or theory-free RCTs, or even just ‘estimation of effect sizes’. Science is about constructing models of how things work. But sometimes the facts are indeed so bizarre in the light of previous knowledge that you cannot ignore them because without these ‘new facts’ you can’t build subsequent theories. Darwin and much of natural history stands as an example, here, but my personal favourite is that provided by the great biochemist Erwin Chargaff in the late 1940s. Wikipedia describes the first of his ‘rules’.

The first parity rule was that in DNA the number of guanine units is equal to the number of cytosine units, and the number of adenine units is equal to the number of thymine units.

Now, in one sense a simple observation (C=G and A=T), with no causal theory. But run the clock on to Watson and Crick (and others), and see how this ‘fact’ gestated an idea that changed the world.

  1. The original work was on surgical procedures undertaken by surgeons. Medicine has changed, and now physicians undertake many invasive procedures, and I suspect the same trends would be evident.
  2. Yes, you can go a lot deeper on this topic and add in more nuance.
  3. Their book on this topic is Deaths of Despair and the Future of Capitalism published by Princeton Universty Press.

Breaking bad

by reestheskin on 02/11/2020

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From this week’s Economist | Breaking through

Yet nowhere too little capital is being channelled into innovation. Spending on R&D has three main sources: venture capital, governments and energy companies. Their combined annual investment into technology and innovative companies focused on the climate is over $80bn. For comparison, that is a bit more than twice the R&D spending of a single tech firm, Amazon.

Market and state failure may go together. Which brings me back to Stewart Brand’s idea of Pace Layering

Education is intellectual infrastructure. So is science. They have very high yield, but delayed payback. Hasty societies that can’t span those delays will lose out over time to societies that can. On the other hand, cultures too hidebound to allow education to advance at infrastructural pace also lose out.

Pace Layering: How Complex Systems Learn and Keep Learning

I won’t even mention COVID-19.

Fail. Fail again. Fail better.

by reestheskin on 28/10/2020

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I came across a note in my diary from around fifteen years ago. It was (I assume) after receiving a grant rejection. For once, I sort of agreed with the funder’s decision1. I wrote:

My grant was trivial, at least in one sense. Neils Bohr always said (or words to the effect) that the job of science was to reduce the profound to the trivial. The ‘magical’ would be made the ordinary of the everyday. My problem was that I started with the trivial.

As for the merits of review: It’s the exception that proves the rule.

  1. Bert Vogelstein, who I collaborated with briefly in the 1990s, after seeing our paper initially rejected by the glossy of the day , informed me that the only sensible personal strategy was to believe that reviewers are always wrong.

Human origins: just a little messy

by reestheskin on 06/10/2020

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Nice article in the Economist on how our ideas about speciation have been revised and updated. And not just for those animals but for humans too. In their words:

To be human, then, is to be a multispecies mongrel.

Following the science

by reestheskin on 03/10/2020

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That “scientific management” bungled the algorithm for children’s exam results, verifies a maxim attributed to J.R. Searle, an American philosopher: if you have to add “scientific” to a field, it probably ain’t.

AD.Pellegrini in a letter to the Economist.

I have written elsewhere about this in medicine and science. We used to have physiology, but now some say physiological sciences; we used to have pharmacology, but now often see pharmacological sciences1. And as for medicine, neurology and neurosurgery used to be just fine, but then the PR and money grabbing started so we now have ‘clinical neuroscience’ — except it isn’t. As Herb Simon pointed out many years ago, the professions and professional practice always lose out in the academy.

  1. Sadly, my old department in Newcastle became Dermatological Sciences, and my most recent work address is Deanery of Clinical Sciences — which means both nouns are misplaced.

The way Brenner sees the world

by reestheskin on 29/09/2020

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Alas, there will no more new ones of these, as arguably the greatest of modern biology’s experimentalists, Sydney Brenner, passed away last year. One of his earlier quotes — the source I cannot find at hand — was that it is important in science to be out of phase. You can be ahead of the curve of fashion or possibly, better still, be behind it. But stay out of phase. So, no apologies for being behind the curve on these ones which I have just come across.

Sydney Brenner remarked in 2008, “We don’t have to look for a model organism anymore. Because we are the model organisms.”

Sydney Brenner has said that systems biology is “low input, high throughput, no output” biology.

Quoted in The science and medicine of human immunology | Science

Image source and credits via WikiCommons

As light as a bag of wind

by reestheskin on 25/09/2020

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In my ignorance I had always assumed that the ‘Haldane’ of the Haldane Principle1 referred to the great and singular geneticist and physiologist JBS Haldane. Not true. JBS once remarked that God must have been inordinately fond of beetles because there are so many species of beetles, so with the Haldanes; (good) fortune is, it appears, inordinately fond of the Haldane clan. A relative of JBS, Richard Burdon Haldane — who did indeed come up with the Haldane principle — is the subject of a new biography by Philip Campbell, and a witty and sharp review in the FT by Philip Stephens.

Watching today’s politicians fall over their own mistakes as they fumble with the Covid-19 pandemic, it is easy to forget that securing high office once required more than a few years of dashing off political columns for a national newspaper. So the life and political times of Richard Haldane, the subject of John Campbell’s engaging biography, offers a fitting rebuke to the trivial mendacity and downright incompetence of the nation’s present administration.

Exaggeration, it is not. Haldane…

…an Edinburgh lawyer and philosopher-politician before becoming a minister in Herbert Asquith’s Liberal administrations, was an important champion of universal education and one of the founding fathers of the UK university system. He also found time to create the Territorial Army, and to have a hand in the foundation of the London School of Economics, the Medical Research Council and the Secret Intelligence Service…

As Asquith’s minister for war, he created the expeditionary force that saved Britain from defeat in the opening stages of the first world war. As Lord Chancellor, his judgments did much to set in place the federalist tilt of the Canadian constitution.

And if there is any doubt about his intellectual gravitas, the review is headed by an image of Haldane with Albert Einstein whom he hosted on the latter’s first visit to the UK in the 1920s. Just conjure up BoJo or Patel or Hancock when you read the above, or when you step on something unpleasant and slimy.

It also seems that Haldane might have performed slightly better across the dispatch box than some of the current irregulars. Clark McGinn writes

He [Haldane] is also one of the few men to have beaten Winston Churchill by riposte. Haldane was a portly figure and Churchill remarked on his girth by asking when the baby was due and what it would be called. Haldane retorted: “If it’s a boy it will be George after the King, a girl will be Mary after the Queen. But if it is just wind I shall call it Winston.”

  1. The Haldane Principle is the idea that decisions about what to spend research funds on should be made by researchers instead of politicians. It is named after Richard Burdon Haldane. For a recent take on the Haldane Principle see David Edgerton, The ‘Haldane Principle’ and other invented traditions in science policy here.

In the year of the plague 1666

by reestheskin on 03/08/2020

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I procured me a Triangular glass-Prisme, to try therewith the celebrated Phenomena of Colours. And in order thereto having darkened my chamber and made a small hole in my window-shuts, to let in a convenient quantity of the Suns light…but I surprised to see them in an oblong form; which, according to the received laws of Refraction, I expected should have been circular.

Well, Isaac Newton obviously had better functioning shutters than my bedroom blackout blinds. Most summer mornings (which at this latitude last much of the night…) I receive — without choice — lessons in physics 101. Here are some iPhone shots from this morning. The quote says a lot about science: note the terms, convenient quantity, surprised and expected.

Politics as a class of dominant negative mutation

by reestheskin on 29/07/2020

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Today many scientists describe their research as apolitical, but Haldane knew that was impossible: ‘I began to realise that even if the professors leave politics alone, politics won’t leave the professors alone.’

From a review in the Economist of a biography of JBS Haldane by Samanth Subramanian.

Two things to add. Haldane’s paper A Defense of Beanbag Genetics is a personal favourite, but sticking with the genetics theme, I think of politics, and many politicians, as examples of dominant negative mutations.

No just in time here

by reestheskin on 16/07/2020

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“I hope the lesson will really be that we can’t afford as a society to create the fire brigade once the house is on fire. We need that fire brigade ready all the time hoping that it never has to be deployed.”

Peter Piot 1

No just in time here. It’s in the statistical tails that dragons lurk and reputations are shattered. Chimes with a quote from Stewart Brand that I posted a short while back.

Education is intellectual infrastructure. So is science. They have very high yield, but delayed payback. Hasty societies that can’t span those delays will lose out over time to societies that can. On the other hand, cultures too hidebound to allow education to advance at infrastructural pace also lose out.

  1. (Virologist Peter Piot,  co-discoverer of  Ebola and who worked on treating and preventing HIV, talking about getting COVID-19 on his institution’s podcast. (London School of Hygiene & Tropical Medicine podcast )

Mathiness, scientism and give me the money.

by reestheskin on 06/07/2020

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Two nice quotes from Paul Romer about his paper Mathiness in the Theory of Economic Growth

The alternative to science is academic politics, where persistent disagreement is encouraged as a way to create distinctive sub-group identities.

The usual way to protect a scientific discussion from the factionalism of academic politics is to exclude people who opt out of the norms of science. The challenge lies in knowing how to identify them.

I can agree go along with both, but it is in the details that the daemons feast. It appears to me that the ‘norms of science’ argument is itself problematic, reminding me of those silly things you learn at school about the scientific method 1. The historical origin of the concept of the scientific method owed more to attempts to brand certain activities in the eyes of those who were not practicing scientists 2. As a rough approximation, the people who talk about the scientific method tend not to do science. Of course, in more recent times, the use of the term ‘science’ itself has been a flag for obtaining funding, status or approval. Dermatology is now dermatological sciences ; pharmacology is now pharmacological sciences. Even more absurd, in the medical literature I see the term delivery science (and I don’t mean Amazon), or reproducibility science. The demarcation of science from non-science is a hard philosophical problem going back way before Popper; I will not solve it. The danger is that we might end up exiling all those meaningful areas of human rationality that we once — rightly — considered outwith science, but still valued. There is indeed a subject that we might reasonably call medical science(s). It is just not synonymous with the principles and practice of medicine. It is also why political economy is a more useful subject than economics (or worse still, economic sciences).

  1. I guess this depends on how you interpret the ‘they’ in Romer’s second quote. It is the people or the norms that are the problem? I tend to think of both.
  2. There is an excellent recent article in the New York Review of Books that touches upon this issue Just Use Your Thinking Pump! by Jessica Riskin.

On being an eternal student.

by reestheskin on 22/06/2020

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Freeman Dyson died February 28th this year. There are many obituaries of this great mind and eternal rebel. His book, Disturbing the Universe, is for me one of a handful that gets the fundamental nature of discovery in science and how science interacts with other modes of being human. His intellectual bravery and honesty shine through most of his writings. John Naughton had a nice quote from him a short while back.

Some mathematicians are birds, others are frogs. Birds fly high in the air and survey broad vistas of mathematics out to the far horizon. They delight in concepts that unify our thinking and bring together diverse problems from different parts of the landscape. Frogs live in the mud below and see only the flowers that grow nearby. They delight in the details of particular objects, and they solve problems one at a time. I happen to be a frog, but many of my best friends are birds. The main theme of my talk tonight is this. Mathematics needs both birds and frogs.

In truth he was both frog and an albatross. Here are some words from his obituary in PNAS.

During the Second World War, Dyson worked as a civilian scientist for the Royal Air Force’s Bomber Command, an experience that made him a life-long pacifist. In 1941, as an undergraduate at Trinity College, Cambridge, United Kingdom, he found an intellectual role model in the famed mathematician G. H. Hardy, who shared two ideas that came to define Dyson’s trajectory: “A mathematician, like a painter or a poet, is a maker of patterns,” and “Young men should prove theorems; old men should write books.”

Heeding the advice of his undergraduate mentor, Dyson returned to his first love of writing. He became well-known to a wide audience by his books Disturbing the Universe (1979) (1) and Infinite in All Directions (1988) (2), and his many beautiful essays for The New Yorker and The New York Review of Books. In 2018, he published his autobiography, Maker of Patterns (3), largely composed of letters that he sent to his parents from an early age on.

And as for us eternal students, at least I have one thing in common.

…Dyson never obtained an official doctorate of philosophy. As an eternal graduate student, a “rebel” in his own words, Dyson was unafraid to question everything and everybody. It is not surprising that his young colleagues inspired him the most.

Freeman J. Dyson 1923–2020: Legendary physicist, writer, and fearless intellectual explorer | PNAS

Queerer that I can imagine

by reestheskin on 16/06/2020

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Its natural, Jim. From an obituary of Julian Perry Robinson in Nature

Julian Perry Robinson (1941–2020)

In 1981, the US government publicly accused Soviet-backed forces in southeast Asia of waging toxin warfare and violating their legal obligations under the 1925 Geneva Protocol and 1972 Biological Weapons Convention. It alleged that aircraft dispersed ‘yellow rain’ containing mycotoxins that were “not indigenous to the region”. Julian Perry Robinson, working alongside biologist Matthew Meselson at Harvard University in Cambridge, Massachusetts, established that what actually fell was wild-honeybee faeces containing naturally occurring toxins. He died on 22 April, aged 78.

Prose

by reestheskin on 09/06/2020

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The Nobel laureate David Hubel commented somewhere that reading most modern scientific papers was like chewing sawdust. Certainly it is rare nowadays to see the naked honesty of Watson and Crick’s classic opening paragraphs, or the melody not being drowned out by the the metrical percussion.

WE wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest [emphasis added].

A structure for nucleic acid has already been proposed by Pauling and Corey1. They kindly made their manuscript available to us in advance of publication. Their model consists of three intertwined chains, with the phosphates near the fibre axis, and the bases on the outside. In our opinion, this structure is unsatisfactory for two reasons : (1) We believe that the material which gives the X-ray diagrams is the salt, not the free acid. Without the acidic hydrogen atoms it is not clear what forces would hold the structure together, especially as the negatively charged phosphates near the axis will repel each other. (2) Some of the van der Waals distances appear to be too small.

And then there is that immortal understated penultimate paragraph.

It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.

Well here is another one that impresses me even if I can claim no expertise in this domain. It is from the prestigious journal Physical Review, is 27 words in length, with one number, one equation and one reference.  Via Fermat’s Library @fermatslibrary

 

 

 

 

 

Via Fermat’s Library @fermatslibrary

The slow now

by reestheskin on 18/05/2020

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Education is intellectual infrastructure.  So is science.  They have very high yield, but delayed payback.  Hasty societies that can’t span those delays will lose out over time to societies that can.  On the other hand, cultures too hidebound to allow education to advance at infrastructural pace also lose out.

Stewart Brand.

Almost queerer than we can imagine

by reestheskin on 24/04/2020

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Some non-covid-19 recreational reading. Although the bees might be here longer than us..

Hive Mentalities | by Tim Flannery | The New York Review of Books

According to Thor Hanson’s Buzz, the relationship between bees and the human lineage goes back three million years, to a time when our ancestors shared the African savannah with a small, brownish, robin-sized bird—the first honeyguide. Honeyguides are very good at locating beehives, but they are unable to break into them to feed on the bee larvae and beeswax they eat. So they recruit humans to help, attracting them with a call and leading them to the hive. In return for the service, Africans leave a small gift of honey and wax: not enough that the bird is uninterested in locating another hive, but sufficient to make it feel that its efforts have been worthwhile. Honeyguides may have been critical to our evolution: today, honey contributes about 15 percent of the calories consumed by the Hadza people—Africa’s last hunter-gatherers—and because brains run on glucose, honey located by honeyguides may have helped increase our brain size, and thus intelligence.

Review of Buzz: The Nature and Necessity of Bees

by Thor Hanson. Basic Books.

Dan Greenberg RIP

by reestheskin on 17/04/2020

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Daniel S. Greenberg (1931–2020) has died. Nice obituary about him and why he mattered in this week’s Science.

Daniel S. Greenberg (1931–2020) | Science

At the time, the idea of a journalist-written section in a publication devoted to publishing research papers was highly unusual, and so was the approach that Dan and his team took. They covered basic research policy in much the same way a business reporter would cover development of economic policy: as a set of competing interests…[emphasis added].

However, it was not greeted with universal enthusiasm. In a preface to the second edition, Dan noted that it sparked “reactions that flowed from the belief that the scientific community should be exempt from the types of journalistic inquiries that are commonplace to other segments of our society.” He called that attitude “nonsense.”

No old (nor broken) records here

by reestheskin on 21/03/2020

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Richard Horton in the Lancet writes:

Imagine if the entire edifice of knowledge in medicine was built upon a falsehood. Systematic reviews are said to be the highest standard of evidence-based health care. Regularly updated to ensure that treatment decisions are built on the most up-to-date and reliable science, systematic reviews and meta-analyses are widely used to inform clinical guidelines and decision making. Powerful organisations have emerged to construct a knowledge base in medicine underpinned by the results of systematic reviews. One such organisation is Cochrane, with 11 000 members in over 130 countries. This extraordinary movement of people is justifiably passionate about the idea that it is contributing to better health outcomes for everyone, everywhere. The industry that drives the production of systematic reviews today is financed by some of the most influential agencies in medical research. Cochrane, for example, points to three funders providing over £1 million each—the UK’s National Institute for Health Research (NIHR), the US National Institutes of Health (NIH), and Australia’s National Health and Medical Research Council (NHMRC).

Well, it really is a bit late for all this soul searching. See my earlier post here ‘Mega-silliness’ (commenting on what others had already pointed out); or my Evidence Based Medicine: the Epistemology That Isn’t, written over 20 years ago;  and my contribution to the wake (even if I didn’t put my hand in my pocket), Why we should let “evidence-based medicine” rest in peace. The genesis of EBM was as a cult whose foundational myth was that P values could act as a true machine. Those followers who had originally hoped for a place in the promised afterlife, soon settled for paying the bills, and EBM morphed into a career opportunity for those who found accountancy too daring. So, pace John Mayall on Jazz Blues Fusion, don’t come here to listen to an old record. I promise.

Offline: The gravy train of systematic reviews – The Lancet

Tidying up

by reestheskin on 04/03/2020

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I have spend a lot of time recently sifting through the detritus of a career. Finally — well, I hope, finally — I have managed to sort out my books. All neatly indexed in Delicious Library, and now for once the virtual location mirrors the physical location. For how long I do not know. Since I often buy books based on reviews, I used to put a copy of the review in with the book (a habit I have dropped but need to restart). I rediscovered this one by David Colquhoun (DC) reviewing ‘The Diet Delusion’ by Gary Taubes in the BMJ (with the unexpurgated text on his own web site).

I am a big fan of DC as he has lived though the rise and decline of much higher education in the UK. And he remains fearless and honest, qualities that are not always at the forefront of the modern university. Quoting the great Robert Merton he writes:

“The organization of science operates as a system of institutionalized vigilance, involving competitive cooperation. In such a system, scientists are at the ready to pick apart and assess each new claim to knowledge. This unending exchange of critical appraisal, of praise and punishment, is developed in science to a degree that makes the monitoring of children’s behavior by their parents seem little more than child’s play”.

He adds:

“The institutionalized vigilance, “this unending exchange of critical judgment”, is nowhere to be found in the study of nutrition, chronic disease, and obesity, and it hasn’t been for decades.”

On Taubes and his (excellent book):

It took Taubes five years to write this book, and he has nothing to sell apart from his ideas. No wonder it is so much better than a scientist can produce. Such is the corruption of science by the cult of managerialism that no university would allow you to spend five years on a book

(as would be expected the BMJ omitted the punch line — they would, wouldn’t they?)

There is also a neat quote from Taubes in one of the comments on DC’s page from Beth@IDblog, one that I will try hard not to forget:

Taubes makes a point at the end of the Dartmouth medical grand rounds video that I think is important: “I’m not trying to convince you that it’s true, I’m trying to convince you that it should be taken seriously.”

Before reproducibility must come preproducibility

by reestheskin on 10/02/2020

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This is an article by Philip Stark in Nature published awhile back. I like it.

In 1992, philosopher Karl Popper wrote: “Science may be described as the art of systematic oversimplification — the art of discerning what we may with advantage omit.” What may be omitted depends on the discipline.

You can say this another way: all experiments do violence to the natural world. We always want to cleave at the joints. But doing so may lead to error.

In 1992, philosopher Karl Popper wrote: “Science may be described as the art of systematic oversimplification — the art of discerning what we may with advantage omit.” What may be omitted depends on the discipline. Results that generalize to all universes (or perhaps do not even require a universe) are part of mathematics. Results that generalize to our Universe belong to physics. Results that generalize to all life on Earth underpin molecular biology. Results that generalize to all mice are murine biology. And results that hold only for a particular mouse in a particular lab in a particular experiment are arguably not science.

Science should be ‘show me’, not ‘trust me’; it should be ‘help me if you can’, not ‘catch me if you can’. If I publish an advertisement for my work (that is, a paper long on results but short on methods) and it’s wrong, that makes me untrustworthy. If I say: “here’s my work” and it’s wrong, I might have erred, but at least I am honest.

In medicine we have particular problems. Repeating experiments in model organisms is often possible whereas in man things are much harder. There is an awful lot of published medical research that is not a reliable guide to action.

Before reproducibility must come preproducibility

On one word after another

by reestheskin on 28/01/2020

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Well, I doubt if any readers of these scribblings will be shocked. After all TIJABP. But this piece by the editor of PNAS wonders if the day of meaningful editing is over. I hope not. Looking backwards over my several hundred papers, the American Journal of Human Genetics was the most rigorous and did the most to improve our manuscript.

On a subject no one wants to read about (about which no one wants to read?) | PNAS

“Communication” remains in the vocabulary of scientific publishing—for example, as a category of manuscript (“Rapid Communications”) and as an element of a journal name (Nature Communications)—not as a vestigial remnant but as a vital part of the enterprise. The goal of communicating effectively is also why grammar, with its arcane, baffling, or even irritating “rules,” continues to matter. With the rise of digital publishing, attendant demands for economy and immediacy have diminished the role of copyeditor. The demands are particularly acute in journalism. As The New York Times editorial board member Lawrence Downs (4) lamented, “…in that world of the perpetual present tense—post it now, fix it later, update constantly—old-time, persnickety editing may be a luxury…. It will be an artisanal product, like monastery honey and wooden yachts.” Scientific publishing is catching up to journalism in this regard.

One thing I won’t miss in retirement

by reestheskin on 27/01/2020

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Being a renowned scientist doesn’t ensure success. On the same day that molecular biologist Carol Greider won a Nobel prize in 2009, she learnt that her recently submitted grant proposal had been rejected. “Even on the day when you win the Nobel prize,” she said in a 2017 graduation speech at Cold Spring Harbor Laboratory in New York, “sceptics may question whether you really know what you’re doing.”

Secrets to writing a winning grant

You don’t have to be mad to read this

by reestheskin on 13/01/2020

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There is an interesting review in the Economist of the ‘Great Pretender: The Undercover Mission that Changed out Understanding of Madness,’ written by Susan Cahalan. The book is the story of the American psychologist David Rosenhan who “recruited seven volunteers to join him in feigning mental illness, to expose what he called the ‘undoubtedly counter-therapeutic’ culture of his country’s psychiatry”.

Rosenthal’s studies are well known and were influential, and some might argue that may have had have a beneficial effect on subsequent patient care. The question is whether they were true. The review states:

in the end Rosenham emerges as an unpalatable symptom of a wider academic malaise”.

As for the ‘malaise’, the reviewer goes on:

Many of psychology’s most famous experiments have recently been discredited or devalued, the author notes. Immense significance has been attached to Stanley Milgram’s shock tests and Philip Zimbardo’s Stanford prison experiment, yet later re-runs have failed to reproduce their findings. As Ms Cahalan laments, the feverish reports on the undermining of such theories are a gift to people who would like to discredit science itself.

I have a few disjointed thoughts on this. There are plenty of other considered critiques of the excesses of modern medical psychiatry. Anthony Clare’s ‘Psychiatry in Dissent’ was for me the best introduction to psychiatry. And Stuart Sutherland’s “Breakdown’ was a blistering and highly readable attack on medical (in)competence as much as the subject itself (Sutherland was a leading experimental psychologist, and his account is autobiographical). And might the cross-country diagnostic criteria studies not have happened without Rosenham’s work?

As for undermining science (see the quote above), I think unreliable medical science is widespread, and possibly there is more of it than in many past periods. Simple repetition of experiments is important but not sufficient, and betrays a lack of of understanding of why some science is so powerful.

Science owes its success to its social organisation: conjectures and refutations, to use Popper’s terms, within a community. Just repeating an experiment under identical conditions is not sufficient. Rather you need to use the results of one experiment to inform the next, and with the accumulation of new results, you need to build a larger and larger edifice which whilst having greater explanatory power is more and more intolerant of errors at any level. Building large structures out of Lego only works because of the precision engineering of each of the component bricks. But any errors only become apparent when you add brick-on-brick. When a single investigator or group of investigators have skin in the game during this process — and where experimentation is possible — science is at its strongest (the critiques can of course come from anywhere).

An alternative process is when the results of a series of experiments are so precise and robust that everyday life confirms them: the lights go on when I click the switch. This harks back to the reporting of science as ‘demonstrations’.

By these two standards much medical science may be unreliable. First, because the fragmentation of enquiry discourages the creation of broad explanatory theories or tests of the underlying hypotheses. The ‘testing’ is more whether a publishable unit can be achieved rather than nature understood. Second, in many RCTs or technology assessments there is little theoretical framework on which to challenge nature. Nor can everyday practice act as the necessary feedback loop in the way the tight temporal relationship between flipping the switch and seeing the light turn on can.

We need more STEM (STEAM etc)

by reestheskin on 08/01/2020

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Perhaps, perhaps not. But when and where is even more important.

Hailed as a maths prodigy at school, Shields accepted a junior position at Merrill Lynch after studying engineering, economics and management at Oxford University because the trading room floor offered him a thrilling, dynamic environment. He was not alone: of 120 engineers in his year group at university, Shields added, only five went into engineering.

I think we should be much more cautious in attempting to direct young people’s choices beyond providing them with an education. We should feel proud of their independence of mind, remembering that supply side factors will likely win out over central planning. It is the supply side that we need to deal with, not least Putts Law. The same applies to medicine.

This personal story is worth a read for other lessons, too.

‘The men who plundered Europe’: bankers on trial for siphoning €60bn | Business | The Guardian

On not being the Queen of Sciences

by reestheskin on 16/12/2019

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“If biology is difficult, it is because of the bewildering number and variety of things one must hold in one’s head”.
John Maynard Smith (1977).

Leo Szilard recalled, that when he did physics he could lounge in the bath for hours and hours, just thinking. Once he moved into biology things were never the same: he was always having to get out to check some annoying fact. Dermatology is worse, trust me.

A time for everything

by reestheskin on 22/10/2019

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Terrific interview with Sydney Brenner about the second greatest scientific revolution of the 20th century.

I think it’s really hard to communicate that because I lived through the entire period from its very beginning, and it took on different forms as matters progressed. So it was, of course, wonderful. That’s what I tell students. The way to succeed is to get born at the right time and in the right place. If you can do that then you are bound to succeed. You have to be receptive and have some talent as well…

To have seen the development of a subject, which was looked upon with disdain by the establishment from the very start, actually become the basis of our whole approach to biology today. That is something that was worth living for.

This goes for more than science and stretches out into far more mundane aspects of life. Is there any alternative?

Kings Review

Job of an academic

by reestheskin on 06/09/2019

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Whatever the context(s) of these events, the words are right.

The job of a scientist is to look for the truth, and the job of a teacher is to help people to empower themselves. I failed to do my job on both counts.

It is however not just the job of scientists.

I am writing to apologize to Jeffrey Epstein’s victims